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Biomedical subjects

C J Roberts

Publications and source records attributed to C J Roberts.

At least 19 recordsLinked to original sources
PubMed1995

In vivo inhibition of oestrone sulphatase and dehydroepiandrosterone sulphatase by oestrone-3-O-sulphamate.

Many tumours in endocrine-sensitive tissues, such as the breast and endometrium, are hormone-dependent and the hydrolysis of oestrone sulphate (EIS) to oestrone by oestrone sulphatase (EI-STS) is a major source of oestrogen in such tumours. Oestrone-3-O-sulphamate (EMATE) has been shown to be a potent EI-STS inhibitor in vitro, and in this study its ability to inhibit enzyme activity in vivo was examined. EMATE was initially administered to female rats for 7 days, after which liver EI-STS activity was measured. As EMATE also inhibits a related sulphatase in vitro, dehydroepiandrosterone sulphatase (DHA-STS), its effect on the activity of this enzyme in vivo was also investigated. DHA-STS has a pivotal role in regulating the synthesis of another steroid with potent oestrogenic properties, androstenediol. Administration of EMATE almost completely inhibited liver EI-STS (99%) and DHA-STS (99%) activities and was active when given by the oral or subcutaneous routes. After a single dose of EMATE or following the cessation of multiple doses for 10 days, liver EI-STS activity remained inhibited ( > 95%) for up to 7 and 10 days, respectively. Other compounds, such as 4-hydroxytamoxifen and the "pure" antioestrogen ICI 182,780, which are reported to inhibit EI-STS activity in vitro, did not inhibit activity in vivo. In a preliminary study, EMATE, when injected over a 12-day period, effectively reduced the growth of EIS-stimulated nitrosomethyl-urea-induced mammary tumours in ovariectomised rats and inhibited tumour sulphatase activity in treated animals.

Animals↗
PubMed1995

Improving the primary management of emergency surgical admissions: a controlled trial.

The initial screening by senior surgical staff of surgical patients referred for emergency hospital admission should result in improved patient management. The present study was undertaken to determine the effects of this policy. The primary outcome measure was hospital admission rates. The number of operations, diagnostic investigations, initial treatments, deaths, length of stay and bed days per 100 referrals were also measured. The results suggest a 20 per cent reduction in emergency surgical admissions, an important potential benefit to the health service, and to individual patients.

Adult↗
PubMed1993

Abnormal chromosome behavior in Neurospora mutants defective in DNA methylation.

The function and regulation of DNA methylation in eukaryotes remain unclear. Genes affecting methylation were identified in the fungus Neurospora crassa. A mutation in one gene, dim-2, resulted in the loss of all detectable DNA methylation. Abnormal segregation of the methylation defects in crosses led to the discovery that the methylation mutants frequently generate strains with extra chromosomes or chromosomal parts. Starvation for S-adenosylmethionine, the presumed methyl group donor for DNA methylation, also produced aneuploidy. These results suggest that DNA methylation plays a role in the normal control of chromosome behavior.

5-Methylcytosine↗
PubMed1992

Topographical investigations of human ovarian-carcinoma polymorphic epithelial mucin by scanning tunnelling microscopy.

Human polymorphic epithelial mucin is a high-molecular-mass glycoprotein that associates to provide protection to the epithelial-cell surface and may afford the malignant cell a selective advantage for growth. The scanning-tunnelling-microscopy micrographs obtained in the present study identify the purified human ovarian-carcinoma polymorphic epithelial mucin glycoproteins as rod-shaped molecules of mixed length. The dimensions of the individual molecules range from 25 to 45 nm in length and are 3-4 nm in width. The images further suggest that lateral association of the rods occurs.

Animals↗
PubMed1992

Nitrendipine and renal tubular function in human volunteers.

Nine normotensive, water-loaded subjects received 10 mg oral nitrendipine, and eight subjects received placebo in a double-blind randomized manner. Urine and plasma were collected at fixed time points for 1 hour before and for 4 hours after drug administration for biochemical measurements. Glomerular filtration rate was measured by inulin clearance and effective renal blood flow was measured by para-amino hippurate clearance. Absolute sodium excretion increased by 25.9% from 0.27 +/- 0.03 mmol/min to 0.34 +/- 0.02 mmol/min (P = .02), and fractional sodium excretion increased by 32.3% from 18.9 +/- 3.0% to 25.0 +/- 1.9% (P = .03) after nitrendipine, but both were unchanged after placebo. There was no change in inulin clearance, para-amino hippurate clearance, urine volume, or fractional excretion of uric acid, which made an effect on glomerular filtration, renal blood flow, or proximal tubular function an unlikely explanation of the natriuresis. Fractional excretion of magnesium increased after both placebo and nitrendipine administration, from 5.0 +/- 0.6% to 6.8 +/- 0.7% (P = .027) and 5.7 +/- 0.8% to 8.8 +/- 1.0% (P = .006), respectively. Fractional excretion of phosphate also increased after both placebo and nitrendipine, from 9.5 +/- 2.3% to 12.9 +/- 3.9% (P = .05) and 9.7 +/- 1.7% to 14.2 +/- 1.9% (P = .002), respectively. These changes are likely to be due to the effects of the water load rather than due to a drug effect. There was no change in clearance of solute free water, which made a direct effect on the loop of Henle or cortical diluting segment unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Membrane protein sorting in the yeast secretory pathway: evidence that the vacuole may be the default compartment.

The targeting signals of two yeast integral membrane dipeptidyl aminopeptidases (DPAPs), DPAP B and DPAP A, which reside in the vacuole and the Golgi apparatus, respectively, were analyzed. No single domain of DPAP B is required for delivery to the vacuolar membrane, because removal or replacement of either the cytoplasmic, transmembrane, or lumenal domain did not affect the protein's transport to the vacuole. DPAP A was localized by indirect immunofluorescence to non-vacuolar, punctate structures characteristic of the yeast Golgi apparatus. The 118-amino acid cytoplasmic domain of DPAP A is sufficient for retention of the protein in these structures, since replacement of the cytoplasmic domain of DPAP B with that of DPAP A resulted in an immunolocalization pattern indistinguishable from that of wild type DPAP A. Overproduction of DPAP A resulted in its mislocalization to the vacuole, because cells expressing high levels of DPAP A exhibited vacuolar as well as Golgi staining. Deletion of 22 residues of the DPAP A cytoplasmic domain resulted in mislocalization of the mutant protein to the vacuole. Thus, the cytoplasmic domain of DPAP A is both necessary and sufficient for Golgi retention, and removal of the retention signal, or saturation of the retention apparatus by overproducing DPAP A, resulted in transport to the vacuole. Like wild type DPAP B, the delivery of mutant membrane proteins to the vacuole was unaffected in the secretory vesicle-blocked sec1 mutant; thus, transport to the vacuole was not via the plasma membrane followed by endocytosis. These data are consistent with a model in which membrane proteins are delivered to the vacuole along a default pathway.

Amino Acid Sequence↗
PubMed1990

How good are case notes in the audit of radiological investigations?

Audit based on the use of case notes completed in the ordinary course of patient care has not been widely used because of concern about the completeness and adequacy of such records. This paper describes the results of a study carried out to assess whether information contained in case notes was sufficiently reliable to enable clinical effectiveness to be measured. The study examines the extent to which a radiologist and an epidemiologist agree with two experienced clinicians in making retrospective judgements on whether out-of-hours radiological investigations are worthwhile. There was a high measure of agreement; only a relatively small amount of information in the case notes is needed to make valid judgements on clinical performance. The method described here may be applicable to other diagnostic investigations and the results of the study have wide implications for more effective and efficient management of resources within the NHS.

Clinical Competence↗
PubMed1990

Gastro-oesophageal reflux during elective laparoscopy.

An oesophageal pH electrode was used to record gastro-oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures. No refluxes were recorded during the 63 procedures from which results could be analysed; the upper 95% confidence limit from this observation is 3 in 63 (4.8%). Two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia. Tracheal intubation may be required during laparoscopy, although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless, with the same logic, it is suggested that all patients who hiccough should be intubated.

Adolescent↗
PubMed1990

The effect of propranolol on paracetamol metabolism in man.

Ten healthy volunteers were treated for 4 days with 160 mg propranolol HCl and placebo in random order. At the end of each treatment salivary antipyrine kinetics and the plasma kinetics and urinary excretion of paracetamol and its major metabolites were measured following a 1500 mg oral dose. Propranolol prolonged the half-life of antipyrine by 11 +/- 5% (mean +/- s.e. mean) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol increased the half-life of paracetamol by 25 +/- 12% (P less than 0.05) and lowered its clearance by 14 +/- 3% (P less than 0.05). Propranolol decreased the partial clearance of paracetamol to its cysteine and mercapturate derivatives by 16 +/- 3% (P less than 0.05) and 32 +/- 7% (P less than 0.05), respectively. The partial clearance to the glucuronide conjugate was decreased by 27 +/- 6% (P less than 0.05), whereas that to sulphate was not changed significantly. Propranolol inhibits paracetamol metabolism predominantly through inhibition of the oxidation and glucuronidation pathways.

Acetaminophen↗
PubMed1990

Nitrendipine and the humoral control of sodium homeostasis.

1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P less than 0.001), and mean heart rate increased by 5 beats min-1 (P less than 0.01) after nitrendipine but did not change after placebo. 3. These changes were accompanied by a significant elevation in plasma renin activity (P less than 0.001). A fall in plasma aldosterone following placebo appeared to be attenuated by nitrendipine. Plasma noradrenaline increased to a peak 3 h after nitrendipine administration (P less than 0.05) but did not change following placebo. A fall in the excretion of 6-keto PGF1 alpha following placebo was attenuated by nitrendipine. The total excretion of 6-keto PGF1 alpha after nitrendipine was significantly greater (P less than 0.05) than after placebo but not difference in the total excretion of PGE2 was detected. Nitrendipine did not affect urinary kallikrein excretion. 4. The natriuretic action of nitrendipine is not mediated by the kallikrein-kinin system, but may be related to changes in renal prostaglandins.

Adult↗
PubMed1989

Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease.

The clinical pharmacokinetics of tacrine hydrochloride have been characterized in patients who have Alzheimer's disease. Serum concentrations of the drug and of its probable metabolite were monitored in eight patients after a 25 mg oral dose, in six patients after a 50 mg oral dose, in four patients after repeated administration of 50 mg, and in two patients after a small intravenous dose. Urinary excretion of drug and metabolite for 24 hours was measured in one of the patients who received a small intravenous dose. The serum half-life was 1.59 +/- 0.15 hours (mean +/- SEM) after the 25 mg dose, 2.14 +/- 0.24 hours after the 50 mg dose, and 2.91 +/- 0.39 hours after continuous treatment. After intravenous administration, clearance was above 600 ml/min in both patients, and oral bioavailability was calculated at below 5%. Urine recovery was less than 3% of the dose. The low bioavailability of tacrine hydrochloride is partly explained by presystemic metabolism.

Administration, Oral↗
PubMed1989

Structure, biosynthesis, and localization of dipeptidyl aminopeptidase B, an integral membrane glycoprotein of the yeast vacuole.

We have characterized the structure, biogenesis, and localization of dipeptidyl aminopeptidase B (DPAP B), a membrane protein of the yeast vacuole. An antibody specific for DPAP B recognizes a 120-kD glycoprotein in yeast that behaves like an integral membrane protein in that it is not removed from membranes by high pH Na2CO3 treatment. Inspection of the deduced amino acid sequence of DPAP B reveals a hydrophobic domain near the NH2 terminus that could potentially span a lipid bilayer. The in vitro enzymatic activity and apparent molecular weight of DPAP B are unaffected by the allelic state of PEP4, a gene essential for the proteolytic activation of a number of soluble vacuolar hydrolases. DPAP B is synthesized as a glycosylated precursor that is converted to the mature 120-kD species by carbohydrate addition. The precursor form of DPAP B accumulates in sec mutants (Novick, P., C. Field, and R. Schekman. 1980. Cell. 21:205-215) that are blocked at the ER (sec18) or Golgi apparatus (sec7), but not at secretory vesicles (sec1). Immunolocalization of DPAP B in wild-type or sec1 mutant cells shows that the protein resides in the vacuolar membrane. However, it is present in non-vacuolar compartments in sec18 and sec7 cells, confirming that the delivery of DPAP B is blocked in these mutants. Interestingly, DPAP B appears to stain the nuclear envelope in a sec18 mutant, which is consistent with the accumulation of DPAP B in the ER membrane at the restrictive temperature. These results suggest that soluble and membrane-bound vacuolar proteins use the same stages of the secretory pathway for their transport.

Amino Acid Sequence↗